Evaldsson C, Rydén I, Uppugunduri S
Division of Clinical Chemistry, Department of Biomedicine and Surgery, Linköping University, 581 85 Linköping, Sweden.
Int Immunopharmacol. 2007 Aug;7(8):1025-32. doi: 10.1016/j.intimp.2007.03.008. Epub 2007 Apr 24.
Nucleosides like adenosine, uridine and their nucleotide derivatives (e.g. ATP and UTP) play important roles in many cellular functions, sometimes by acting as signalling molecules through binding to specific P2 nucleotide receptors. P2 receptors are subdivided into P2X and P2Y subfamilies, the latter of which are G-protein coupled receptors. P2Y receptors and nucleoside transporters have been detected in human and rat lungs, where they mediate effects of interest in airway diseases. The aim of this study was to investigate whether uridine has any anti-inflammatory properties in an asthma-like animal model of lung inflammation. The Sephadex-induced lung inflammation model in Sprague-Dawley rats was chosen mainly due to its localised inflammatory response and uridine's limited oral bioavailability. The dextran beads, with or without the addition of uridine, were instilled intratracheally into the lungs, which were excised and examined after 24 h. Sephadex alone led to massive oedema and infiltration of macrophages, neutrophils and eosinophils. Microgranulomas with giant cell formations were clearly visible around the partially degraded beads. Uridine reduced both the oedema and the infiltration of leukocytes significantly, measured as lung wet weight and leukocyte counts in bronchoalveolar lavage fluid, respectively. Uridine appeared to affect the tumour necrosis factor (TNF) levels, although this could not be statistically confirmed due to large variations within the Sephadex control group. We conclude that uridine has anti-inflammatory effects, and that the exact mechanism(s) of action requires further study.
核苷，如腺苷、尿苷及其核苷酸衍生物（如三磷酸腺苷和三磷酸尿苷）在许多细胞功能中发挥着重要作用，有时它们作为信号分子，通过与特定的P2核苷酸受体结合来发挥作用。P2受体可分为P2X和P2Y亚家族，后者是G蛋白偶联受体。已在人和大鼠肺中检测到P2Y受体和核苷转运体，它们在气道疾病中介导相关效应。本研究的目的是探讨尿苷在类似哮喘的肺部炎症动物模型中是否具有抗炎特性。选择Sprague-Dawley大鼠的葡聚糖凝胶诱导的肺部炎症模型，主要是因为其局部炎症反应以及尿苷口服生物利用度有限。将添加或不添加尿苷的葡聚糖珠经气管内注入肺中，24小时后取出肺进行检查。单独的葡聚糖凝胶导致大量水肿以及巨噬细胞、中性粒细胞和嗜酸性粒细胞浸润。在部分降解的珠子周围可见有巨细胞形成的微肉芽肿。尿苷分别以肺湿重和支气管肺泡灌洗液中的白细胞计数来衡量，显著减轻了水肿和白细胞浸润。尿苷似乎影响肿瘤坏死因子（TNF）水平，尽管由于葡聚糖凝胶对照组内存在较大差异，这一点无法得到统计学证实。我们得出结论，尿苷具有抗炎作用，其确切作用机制有待进一步研究。
